Cookies

We use cookies to ensure that we give you the best experience on our website. By continuing to browse this repository, you give consent for essential cookies to be used. You can read more about our Privacy and Cookie Policy.


Durham Research Online
You are in:

Lamina-associated polypeptide 2 alpha regulates cell cycle progression and differentiation via the retinoblastoma-E2F pathway.

Dorner, D. and Vlcek, S. and Foeger, N. and Gajewski, A. and Makolm, C. and Gotzmann, J. and Hutchison, C. J. and Foisner, R. (2006) 'Lamina-associated polypeptide 2 alpha regulates cell cycle progression and differentiation via the retinoblastoma-E2F pathway.', Journal of cell biology., 173 (1). pp. 83-93.

Abstract

Lamina-associated polypeptide (LAP) 2 is a nonmembrane-bound LAP2 isoform that forms complexes with nucleoplasmic A-type lamins. In this study, we show that the overexpression of LAP2 in fibroblasts reduced proliferation and delayed entry into the cell cycle from a G0 arrest. In contrast, stable down-regulation of LAP2 by RNA interference accelerated proliferation and interfered with cell cycle exit upon serum starvation. The LAP2-linked cell cycle phenotype is mediated by the retinoblastoma (Rb) protein because the LAP2 COOH terminus directly bound Rb, and overexpressed LAP2 inhibited E2F/Rb-dependent reporter gene activity in G1 phase in an Rb-dependent manner. Furthermore, LAP2 associated with promoter sequences in endogenous E2F/Rb-dependent target genes in vivo and negatively affected their expression. In addition, the expression of LAP2 in proliferating preadipocytes caused the accumulation of hypophosphorylated Rb, which is reminiscent of noncycling cells, and initiated partial differentiation into adipocytes. The effects of LAP2 on cell cycle progression and differentiation may be highly relevant for the cell- and tissue-specific phenotypes observed in laminopathic diseases.

Item Type:Article
Full text:PDF - Published Version (896Kb)
Status:Peer-reviewed
Publisher Web site:http://dx.doi.org/10.1083/jcb.200511149
Record Created:29 Aug 2008
Last Modified:08 Sep 2011 09:46

Social bookmarking: del.icio.usConnoteaBibSonomyCiteULikeFacebookTwitterExport: EndNote, Zotero | BibTex
Usage statisticsLook up in GoogleScholar | Find in a UK Library